Microfluidics-Enabled Nanovesicle Delivers CD47/PD-L1 Antibodies to Enhance Antitumor Immunity and Reduce Immunotoxicity in Lung Adenocarcinoma

Su, Zhenwei1,2,3; Dong, Shaowei4; Chen, Yao2; Huang, Tuxiong5,6; Qin, Bo7; Yang, Qinhe8; Jiang, Xingyu2; Zou, Chang1,3

2023-05-01

10.1002/advs.202206213

ADVANCED SCIENCE   影响因子和分区

2198-3844

The CD47/PD-L1 antibodies combination exhibits durable antitumor immunity but also elicits excessive immune-related adverse events (IRAEs) caused by the on-target off-tumor immunotoxicity, hindering their clinical benefits greatly. Here, a microfluidics-enabled nanovesicle using ultra-pH-sensitive polymer mannose-poly(carboxybetaine methacrylate)-poly(hydroxyethyl piperidine methacrylate) (Man-PCB-PHEP) is developed to deliver CD47/PD-L1 antibodies (NCPA) for tumor-acidity-activated immunotherapy. The NCPA can specifically release antibodies in acidic environment, thereby stimulating the phagocytosis of bone marrow-derived macrophages. In mice bearing Lewis lung carcinoma, NCPA shows significantly improved intratumoral CD47/PD-L1 antibodies accumulation, promoted tumor-associated macrophages remodeling to antitumoral status, and increased infiltration of dendritic cells and cytotoxic T lymphocytes, resulting in more favorable treatment effect compared to those of free antibodies. Additionally, NCPA also shows less IRAEs, including anemia, pneumonia, hepatitis, and small intestinal inflammation in vivo. Altogether, a potent dual checkpoint blockade immunotherapy utilizing NCPA with enhanced antitumor immunity and reduced IRAEs is demonstrated.

cancer immunotherapy immune-related adverse events microfluidics-enabled nanovesicle ultra-pH-sensitive

SCI ; EI

英语

第一 ; 通讯

Guangdong Basic and Applied Basic Research Foundation["2022A1515110109","2020B1515120032"] ; Guangdong Basic and Applied Basic~Research fund project[2019B1515120033] ; Shenzhen Key Medical Discipline Construction Fund[SZXK053] ; Guangdong Provincial Key Laboratory of Advanced Biomaterials[2022B1212010003] ; Shenzhen Key Laboratory of Smart Healthcare Engineering[ZDSYS20200811144003009]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000980602100001

WILEY

20231914067340

Antigen-antibody reactions ; Biological organs ; Macrophages ; Mammals ; Microfluidics ; Polychlorinated biphenyls ; Tumors

Biological Materials and Tissue Engineering:461.2 ; Immunology:461.9.1 ; Microfluidics:632.5.1 ; Organic Compounds:804.1

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med,Shenzhen Inst Resp Dis,D, Shenzhen 518001, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Dept Biomed Engn, Guangdong Prov Key Lab Adv Biomat, Shenzhen Key Lab Smart Healthcare Engn, 1088 Xueyuan Rd, Shenzhen 518055, Guangdong, Peoples R China
3.Chinese Univ Hong Kong Shenzhen, Sch Med, Life & Hlth Sci, 2001 Longxiang Rd, Shenzhen 518172, Guangdong, Peoples R China
4.Shenzhen Childrens Hosp, Dept Hematol & Oncol, 7019 Yitian Rd, Shenzhen 518038, Guangdong, Peoples R China
5.Shenzhen Univ, Dept Pharmacol, Shenzhen 518060, Guangdong, Peoples R China
6.Shenzhen Univ, Int Canc Ctr, Shenzhen 518060, Guangdong, Peoples R China
7.Cent South Univ, Aier Sch Ophthalmol, Changsha 410083, Hunan, Peoples R China
8.Jinan Univ, Sch Tradit Chinese Med, Guangzhou 510632, Guangdong, Peoples R China

Su, Zhenwei,Dong, Shaowei,Chen, Yao,et al. Microfluidics-Enabled Nanovesicle Delivers CD47/PD-L1 Antibodies to Enhance Antitumor Immunity and Reduce Immunotoxicity in Lung Adenocarcinoma[J]. ADVANCED SCIENCE,2023,10(20).

Su, Zhenwei.,Dong, Shaowei.,Chen, Yao.,Huang, Tuxiong.,Qin, Bo.,...&Zou, Chang.(2023).Microfluidics-Enabled Nanovesicle Delivers CD47/PD-L1 Antibodies to Enhance Antitumor Immunity and Reduce Immunotoxicity in Lung Adenocarcinoma.ADVANCED SCIENCE,10(20).

Su, Zhenwei,et al."Microfluidics-Enabled Nanovesicle Delivers CD47/PD-L1 Antibodies to Enhance Antitumor Immunity and Reduce Immunotoxicity in Lung Adenocarcinoma".ADVANCED SCIENCE 10.20(2023).